Dendritic cells are the canonical professional antigen-presenting cell and are therefore crucial in the generation of efficient adaptive T cell responses. It is now well described that immune cells... Show moreDendritic cells are the canonical professional antigen-presenting cell and are therefore crucial in the generation of efficient adaptive T cell responses. It is now well described that immune cells – including dendritic cells – make drastic changes to their biology to transition between different life stages and to deal efficiently with the threat of infection. However, an unanswered question was if DCs with different T cell polarizing properties - that is to say they preferentially skew T cells towards a specific specialization (for example T helper 1 cells over T helper 2 cells) - rely on distinct metabolic characteristics for their T cell polarizing ability. This thesis tries to address that question by studying the metabolism of dendritic cells after in vitro stimulation with antigens or immunomodulatory compounds that are known to prime either T helper 1 cells, T helper 2 cells, T helper 17 cells or regulatory T cells. In addition, we interrogate the role of liver kinase B1 (LKB1) and mechanistic target of rapamycin complex 1 (mTORC1) in DC biology. Show less
In recent years there have been major advances in our understanding of the role of free fatty acids (FAs) and their metabolism in shaping the functional properties of macrophages and DCs. This... Show moreIn recent years there have been major advances in our understanding of the role of free fatty acids (FAs) and their metabolism in shaping the functional properties of macrophages and DCs. This review presents the most recent insights into how cell intrinsic FA metabolism controls DC and macrophage function, as well as the current evidence of the importance of various exogenous FAs (such as polyunsaturated FAs and their oxidation products-prostaglandins, leukotrienes, and proresolving lipid mediators) in affecting DC and macrophage biology, by modulating their metabolic properties. Finally, we explore whether targeted modulation of FA metabolism of myeloid cells to steer their function could hold promise in therapeutic settings. Show less
